Micro‐Lensed Fiber Laser Desorption Mass Spectrometry Imaging Reveals Subcellular Distribution of Drugs within Single Cells

Abstract

The visualization of temporal and spatial changes in the intracellular environment has great significance for chemistry and bioscience research. Mass spectrometry imaging (MSI) plays an important role because of its unique advantages, such as being label‐free and high throughput, yet it is a challenge for laser‐based techniques due to limited lateral resolution. Here, we develop a simple, reliable, and economic nanoscale MSI approach by introducing desorption laser with a micro‐lensed fiber. Using this integrated platform, we achieved 300 nm resolution MSI and successfully visualized the distribution of various small‐molecule drugs in subcellular locations. Exhaustive dynamic processes of anticancer drugs, including releasing from nanoparticle carriers entering nucleus of cells, can be readily acquired on an organelle scale. Considering the simplicity and universality of this nanoscale desorption device, it could be easily adapted to most of laser‐based mass spectrometry applications.

Insight to Functional Conformation and Noncovalent Interactions of Protein-Protein Assembly Using MALDI Mass Spectrometry

“…Especially, in pandemic time, the need for a fast-response tool to validate specific vaccines can be achieved with MALDI-MS, based on its previous applicability in studies of epitope-antibody interaction analysis. Furthermore, MALDI-mass spectrometry imaging can provide functional and spatial information of protein complex as a part of tissue In this regard, the intracellular spatial resolution in mass spectrometry imaging is developing [140][141][142] and it would be an advance to localize intracellular proteic conformers involved for example in tissue homeostasis where protein conformation controls the organization and dynamics of cell-matrix adhesion [143] as a step forward to a better understanding of tissue chemistry.…”

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

“…The use of t-MALDI-2 MSI system achieved a high pixel size of 600 nm with brain tissue (Niehaus et al, 2019). Besides, as shown in Figure 13, the resolution of recent nano laser probe-based MSI systems can be down to the nm level (subcellular level) by introducing desorption laser with a micro-lensed fiber, proving a great development in MALDI-MSI (Meng et al, 2020). Considering the lack of selectivity of samples of MALDI ionization (Susniak et al, 2020) and the ability to detect DNA (Kirpekar et al, 1999;Ehrich et al, 2005), we believe that MALDI will become more and more important in MSI.…”

“…Furthermore, MALDI ion resources can be easily coupled with high-resolution (resolving power) mass analyzers, such as TOF, FT-ICR, and Orbitrap, which provide high mass accuracy for MSI targets. During the recent years, with the developments of some new MALDI ion sources, such as atmosphere pressure AP-MALDI (Kompauer et al, 2017), AP-SMALDI (Vegvari et al, 2017;Bhandari et al, 2018;Bredehoeft et al, 2019;Kadesch et al, 2020;Mokosch et al, 2021;Mueller et al, 2021;Righetti et al, 2021), MALDI-2 (Soltwisch et al, 2015), transmission MALDI-2 (Niehaus et al, 2019), and nano laser probed-based laser desorption ionization (Meng et al, 2020), the lateral resolution of MALDI-MSI will possibly achieve nm or µm level for single cell and even subcellular scale imaging. Finally, the scanning speed of MALDI-MSI largely depends on the speed of MS detection, spectra recording and data processing.…”

Laser Desorption/Ionization Mass Spectrometry Imaging: A New Tool to See through Nanoscale Particles in Biological Systems

“…Later in 2020, by introducing desorption laser with a micro‐lensed fiber, a nanoscale LDI MSI platform (∼300 nm) for subcellular imaging of drugs and nanocarriers was developed by Hang et al. Using this platform, A dynamic process of anticancer drugs release from nanocarriers in lysosomes and then entering the nucleus finally leading to apoptosis of cancer cells can be distinctly visualized on an organelle scale (Figure 2b) [15] . This novel platform was also applied for mapping drug distribution in a intestine tissue [16] .…”